Maternal creatine in pregnancy: a retrospective cohort study.

OBJECTIVE: To estimate creatine concentrations in maternal plasma and urine, and establish relationships with maternal characteristics, diet and fetal growth. DESIGN: Retrospective cohort study. SETTING: Lyell McEwin Hospital, Adelaide, Australia. POPULATION: A biobank of plasma and urine samples collected at 13, 18, 30 and 36 weeks' gestation from 287 pregnant women from a prospective cohort of asthmatic and non-asthmatic women. METHODS: Creatine was measured by enzymatic analysis. Change in creatine over pregnancy was assessed using the Friedman test. Linear mixed models regression was used to determine associations between maternal factors and diet with creatine across pregnancy and between creatine with indices of fetal growth at birth. MAIN OUTCOME MEASURES: Maternal creatine concentrations, associations between maternal factors and creatine and between creatine and fetal growth parameters. RESULTS: Maternal smoking, body mass index, asthma and socio-economic status were positively and parity negatively associated with maternal plasma and/or urine creatine. Maternal urine creatine concentration was positively associated with birthweight centile and birth length. After adjustment, each µmol/l increase in maternal urinary creatine was associated with a 1.23 (95% CI 0.44-2.02) unit increase in birthweight centile and a 0.11-cm (95% CI 0.03-0.2) increase in birth length. CONCLUSIONS: Maternal factors and fetal growth measures are associated with maternal plasma and urine creatine concentrations. TWEETABLE ABSTRACT: Maternal creatine is altered by pregnancy; fetal growth measures are associated with maternal creatine concentrations.

Muscle Na+-K+-ATPase activity and isoform adaptations to intense interval exercise and training in well-trained athletes.

The Na+ -K+ -ATPase enzyme is vital in skeletal muscle function. We investigated the effects of acute high-intensity interval exercise, before and following high-intensity training (HIT), on muscle Na+ -K+ -ATPase maximal activity, content, and isoform mRNA expression and protein abundance. Twelve endurance-trained athletes were tested at baseline, pretrain, and after 3 wk of HIT (posttrain), which comprised seven sessions of 8 x 5-min interval cycling at 80% peak power output. Vastus lateralis muscle was biopsied at rest (baseline) and both at rest and immediately postexercise during the first (pretrain) and seventh (posttrain) training sessions. Muscle was analyzed for Na+ -K+ -ATPase maximal activity (3-O-MFPase), content ([3H]ouabain binding), isoform mRNA expression (RT-PCR), and protein abundance (Western blotting). All baseline-to-pretrain measures were stable. Pretrain, acute exercise decreased 3-O-MFPase activity [12.7% (SD 5.1), P < 0.05], increased alpha1, alpha2, and alpha3 mRNA expression (1.4-, 2.8-, and 3.4-fold, respectively, P < 0.05) with unchanged beta-isoform mRNA or protein abundance of any isoform. In resting muscle, HIT increased (P < 0.05) 3-O-MFPase activity by 5.5% (SD 2.9), and alpha3 and beta3 mRNA expression by 3.0- and 0.5-fold, respectively, with unchanged Na+ -K+ -ATPase content or isoform protein abundance. Posttrain, the acute exercise induced decline in 3-O-MFPase activity and increase in alpha1 and alpha3 mRNA each persisted (P < 0.05); the postexercise 3-O-MFPase activity was also higher after HIT (P < 0.05). Thus HIT augmented Na+ -K+ -ATPase maximal activity despite unchanged total content and isoform protein abundance. Elevated Na+ -K+ -ATPase activity postexercise may contribute to reduced fatigue after training. The Na+ -K+ -ATPase mRNA response to interval exercise of increased alpha- but not beta-mRNA was largely preserved posttrain, suggesting a functional role of alpha mRNA upregulation.

Effects of creatine supplementation on housekeeping genes in human skeletal muscle using real-time RT-PCR.

The present study examined the validity and reliability of measuring the expression of various genes in human skeletal muscle using quantitative real-time RT-PCR on a GeneAmp 5700 sequence detection system with SYBR Green 1 chemistry. In addition, the validity of using some of these genes as endogenous controls (i.e., housekeeping genes) when human skeletal muscle was exposed to elevated total creatine levels and exercise was also examined. For all except 28S, linear relationships between the logarithm of the starting RNA concentrations and the cycle threshold (C(T)) values were established for beta-actin, beta2-microglobulin (beta2M), cyclophilin (CYC), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We found a linear response between C(T) values and the logarithm of a given amount of starting cDNA for all the genes tested. The overall intra-assay coefficient of variance for these genes was 1.3% and 21% for raw C(T) values and the linear value of 2(-C(T)), respectively. Interassay variability was 2.3% for raw C(T) values and 34% for the linear value of 2(-C(T)). We also examined the expression of various housekeeping genes in human skeletal muscle at days 0, 1, and 5 following oral supplementation with either creatine or a placebo employing a double-blind crossover study design. Treatments were separated by a 5-wk washout period. Immediately following each muscle sampling, subjects performed two 30-s all-out bouts on a cycle ergometer. Creatine supplementation increased (P < 0.05) muscle total creatine content above placebo levels; however, there were no changes (P > 0.05) in C(T) values across the supplementation periods for any of the genes. Nevertheless, 95% confidence intervals showed that GAPDH was variable, whereas beta-actin, beta2M, and CYC were the least varying genes. Normalization of the data to these housekeeping genes revealed variable behavior for beta2M with more stable expressions for both beta-actin and CYC. We conclude that, using real-time RT-PCR, beta-actin or CYC may be used as housekeeping genes to study gene expression in human muscle in experiments employing short-term creatine supplementation combined with high-intensity exercise.

2-Methyl-1,3-dioxaazaspiro[4.5]decanes as novel muscarinic cholinergic agonists.

Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30) behave as weak partial agonists at cholinergic receptors in tissues of limited receptor reserve. The current paper describes the synthesis and biochemical assessment of analogues of AF-30 designed to have sufficient conformational freedom to allow greater receptor flexibility and hence activation. The new compounds and important standards were tested in a new biochemical assay designed to measure both receptor affinity and intrinsic activity of each compound and for their ability to stimulate phosphatidylinositol turnover in rat cerebral cortex. Two azaspirodecanes (5a and 5b) were shown to have far greater predicted efficacy than AF-30.

Synthesis and in vitro biological profile of all four isomers of the potent muscarinic agonist 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane.

The four stereoisomers of the muscarinic agonist 7 have been synthesized from enantiomerically pure exo-azanorbornane esters (13a,b). The esters were obtained in optically active form by separation of the carboxamide diastereomers 12a,b, formed from the borane complex of exo-azanorbornane-3-carboxylate 10 and a chiral amine auxiliary. Using the known chirality of (R)-alpha-methylbenzylamine, an X-ray analysis was accomplished on 12a in order to determine the absolute configuration of the azanorbornane C4 chiral center. Each of the chiral esters 13a,b was separately transformed into the oxadiazoles with concomitant epimerization at C3 of the azanorbornane ring to afford the thermodynamic equilibrium mixture of isomers. Chromatographic separation followed by analysis of each isomer by NMR and GC allowed the absolute stereochemistry of all four isomers of 7 to be confirmed. Full biological evaluation in biochemical and pharmacological assays revealed that the 3R,4R isomer was the most active on receptor binding studies and the most potent on the pharmacological preparations, showing a 50-fold increase in potency at the M2 and M3 sites compared to M1.

Structure-activity relationships of boronic acid inhibitors of dipeptidyl peptidase IV. 1. Variation of the P2 position of Xaa-boroPro dipeptides.

A series of prolineboronic acid (boroPro) containing dipeptides were synthesized and assayed for their ability to inhibit the serine protease dipeptidyl peptidase IV (DPPIV). Inhibitory activity, which requires the (R)-stereoisomer of boroPro in the P1 position, appears to tolerate a variety of L-amino acids in the P2 position. Substitution at the P2 position which is not tolerated include the D-amino acids, alpha,alpha-disubstituted amino acids, and glycine. Specificity against DPPII and proline specific endopeptidase is reported. A correlation between the ability to inhibit DPPIV in cell culture and in the human mixed lymphocyte reaction is demonstrated. A synthesis of prolineboronic acid is reported as well as conditions for generating the fully unprotected boronic acid dipeptides in either their cyclic or acyclic forms.

Novel quinuclidine-based ligands for the muscarinic cholinergic receptor.

Recent clinical studies on Alzheimer's patients have implied that only agents displaying high efficacy at the cortical muscarinic receptor have yielded encouraging results. This paper describes the design, synthesis, and biochemical characterization of novel quinuclidine-based muscarinic agonists which can readily penetrate into the central nervous system and which are capable of displaying high efficacy at cortical sites. With use of a biochemical assay capable of measuring receptor affinity and predicting cortical efficacy, it has been discovered that an oxadiazole ring and related heterocycles can function as bioisosteric replacements for the ester moiety found in several known muscarinic ligands. Within this series there exist compounds which span the efficacy range from high-efficacy agonist through partial agonists to antagonists with affinity comparable or superior to that of classical quaternary ammonium ligands. Consistent with recent molecular biology studies, structure-activity trends are interpreted in terms of separate binding sites for agonists and antagonists with H-bonding interactions characterizing agonist behavior and lipophilic binding characterizing antagonist behavior. Thus the aminooxadiazole moiety has structural features which are optimized for an agonist profile.

Effect of structural modification of enol-carboxamide-type nonsteroidal antiinflammatory drugs on COX-2/COX-1 selectivity.

Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. Substitution at the 6- and 7-positions of the 4-oxo-1,2-benzothiazine-3-carboxamide, alteration of the N-methyl substituent, and amide modification were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothizines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4-dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5.

Creatine supplementation and riluzole treatment provide similar beneficial effects in copper, zinc superoxide dismutase (G93A) transgenic mice.

This study investigated the effects of riluzole (Ril), creatine (Cr) and a combination of these treatments on the onset and progression of clinical signs and neuropathology in an animal model of familial amyotrophic lateral sclerosis, the G93A transgenic mouse (n=13-17 per group). The onset of clinical signs was delayed (P<0.05) by about 12 days in all treatment groups compared with control; however, no differences occurred between treatments. All animals were killed at 199 days of age. At the end of the experimental period the severity of clinical signs was less (P<0.05) with all treatments compared with control. Again no differences between treatments were observed. The treatments had no effect on the number of neurons in ventral horns of the lumbar region of the spinal cord. Transgenic mice ingesting Cr displayed elevated (P<0.05) total Cr levels in cerebral hemispheres (5%) and spinal cord (8%), but not skeletal muscles. These data demonstrate that treatment with Ril and Cr were both effective in delaying disease onset and clinical disability. To the age of killing, no additional benefit was conferred by co-administration of Ril and Cr.

Barriers to adequate delivery of hemodialysis.

Mortality rates among American hemodialysis patients are the highest in the industrialized world. Measures of delivered dialysis (Kt/V) correspond strongly with survival and are estimated to be inadequate in one third of patients. We sought to determine the importance of potential barriers to adequate dialysis, including patient-related and technical factors. Using a cross-sectional study design, we abstracted the charts of 721 randomly selected patients from all 22 chronic hemodialysis units in northeast Ohio. For each of 1,836 treatments provided to these patients, we assessed delivered dialysis (Kt/V) and patient-related factors (ie, hypotension, intradialytic symptoms, and treatment time missed due to noncompliance or transportation problems) and technical factors (ie, dialysis prescription, type of vascular access, clotting, and dialyzer reuse). We used hierarchical regression analysis to determine which potential barriers were independently related to delivered dialysis after adjustment for patient demographic and medical characteristics. Barriers independently related to dialysis delivery (all P values < 0.001) included patient noncompliance, present in 3% of treatments; low dialysis prescription, 14%; use of a catheter for vascular access, 11%; and clotting, 1%. The prevalence of identified barriers varied dramatically across facilities (eg, the prevalence of low dialysis prescription ranged from 0% to 37%, while the prevalence of catheter use ranged from 3% to 28%). In conclusion, patient noncompliance, low dialysis prescription, catheter use, and clotting are the most important barriers to dialysis delivery. Further work is needed to develop interventions to overcome these barriers and to determine the effect of such interventions on dialysis adequacy and patient survival.

Muscle metabolism during prolonged exercise in humans: influence of carbohydrate availability.

Eight endurance-trained men cycled to volitional exhaustion at 69 +/- 1% peak oxygen uptake on two occasions to examine the effect of carbohydrate supplementation during exercise on muscle energy metabolism. Subjects ingested an 8% carbohydrate solution (CHO trial) or a sweet placebo (Con trial) in a double-blind, randomized order, with vastus lateralis muscle biopsies (n = 7) obtained before and immediately after exercise. No differences in oxygen uptake, heart rate, or respiratory exchange ratio during exercise were observed between the trials. Exercise time to exhaustion was increased by approximately 30% when carbohydrate was ingested [199 +/- 21 vs. 152 +/- 9 (SE) min, P < 0.05]. Plasma glucose and insulin levels during exercise were higher and plasma free fatty acids lower in the CHO trial. No differences between trials were observed in the decreases in muscle glycogen and phosphocreatine or the increases in muscle lactate due to exercise. Muscle ATP levels were not altered by exercise in either trial. There was a small but significant increase in muscle inosine monophosphate levels at the point of exhaustion in both trials, and despite the subjects in CHO trial cycling 47 min longer, their muscle inosine monophosphate level was significantly lower than in the Con trial (CHO: 0.16 +/- 0.08, Con: 0.23 +/- 0.09 mmol/kg dry muscle). These data suggest that carbohydrate ingestion may increase endurance capacity, at least in part, by improving muscle energy balance.

Purine loss after repeated sprint bouts in humans.

The influence of the number of sprint bouts on purine loss was examined in nine men (age 24.8 +/- 1.6 yr, weight 76 +/- 3.9 kg, peak O(2) consumption 3.87 +/- 0.16 l/min) who performed either one (B1), four (B4), or eight (B8) 10-s sprints on a cycle ergometer, 1 wk apart, in a randomized order. Forearm venous plasma inosine, hypoxanthine (Hx), and uric acid concentrations were measured at rest and during 120 min of recovery. Urinary inosine, Hx, and uric acid excretion were also measured before and 24 h after exercise. During the first 120 min of recovery, plasma inosine and Hx concentrations, and urinary Hx excretion rate, were progressively higher (P < 0.05) with an increasing number of sprint bouts. Plasma uric acid concentration was higher (P < 0.05) in B8 compared with B1 and B4 after 45, 60, and 120 min of recovery. Total urinary excretion of purines (inosine + Hx + uric acid) was higher (P < 0. 05) at 2 h of recovery after B8 (537 +/- 59 micromol) compared with the other trials (B1: 270 +/- 76; B4: 327 +/- 59 micromol). These results indicate that the loss of purine from the body was enhanced by increasing the number of intermittent 10-s sprint bouts.

Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance.

This study investigated creatine supplementation (CrS) effects on muscle total creatine (TCr), creatine phosphate (CrP), and intermittent sprinting performance by using a design incorporating the time course of the initial increase and subsequent washout period of muscle TCr. Two groups of seven volunteers ingested either creatine [Cr; 6 x (5 g Cr-H(2)O + 5 g dextrose)/day)] or a placebo (6 x 5 g dextrose/day) over 5 days. Five 10-s maximal cycle ergometer sprints with rest intervals of 180, 50, 20, and 20 s and a resting vastus lateralis biopsy were conducted before and 0, 2, and 4 wk after placebo or CrS. Resting muscle TCr, CrP, and Cr were unchanged after the placebo but were increased (P < 0.05) at 0 [by 22.9 +/- 4.2, 8.9 +/- 1.9, and 14.0 +/- 3.3 (SE) mmol/kg dry mass, respectively] and 2 but not 4 wk after CrS. An apparent placebo main effect of increased peak power and cumulative work was found after placebo and CrS, but no treatment (CrS) main effect was found on either variable. Thus, despite the rise and washout of muscle TCr and CrP, maximal intermittent sprinting performance was unchanged by CrS.

Effect of carbohydrate ingestion on glucose kinetics and muscle metabolism during intense endurance exercise.

There has been recent interest in the potential performance and metabolic effects of carbohydrate ingestion during exercise lasting approximately 1 h. In this study, 13 well-trained men ingested in randomized order either a 6% glucose solution (CHO trial) or a placebo (Con trial) during exercise to exhaustion at 83+/-1% peak oxygen uptake. In six subjects, vastus lateralis muscle was sampled at rest, at 32 min, and at exhaustion, and in six subjects, glucose kinetics was determined by infusion of [6,6-(2)H]glucose in both trials and ingestion of [6-(3)H]glucose in the CHO trial. Of the 84 g of glucose ingested during exercise in the CHO trial, only 22 g appeared in the peripheral circulation. This resulted in a small (12 g) but significant (P<0.05) increase in glucose uptake without influencing carbohydrate oxidation, muscle glycogen use, or time to exhaustion (CHO: 68.1+/-4.1 min; Con: 69.6+/-5.5 min). Decreases in muscle phosphocreatine content and increases in muscle inosine monophosphate and lactate content during exercise were similar in the two trials. Although endogenous glucose production during exercise was partially suppressed in the CHO trial, it remained significantly above preexercise levels throughout exercise. In conclusion, only 26% of the ingested glucose appeared in the peripheral circulation. Glucose ingestion increased glucose uptake and partially reduced endogenous glucose production but had no effect on carbohydrate oxidation, muscle metabolism, or time to exhaustion during exercise at 83% peak oxygen uptake.

Influence of sprint training on human skeletal muscle purine nucleotide metabolism.

To examine the effect of sprint training on human skeletal muscle purine nucleotide metabolism, eight active untrained subjects completed a maximal 30-s sprint bout on a cycle ergometer before and after 7 wk of sprint training. Resting muscle ATP and total adenine nucleotide content were reduced (P < 0.05) by 19 and 18%, respectively, after training. Training resulted in a 52% attenuation (P < 0.05) in the magnitude of ATP depletion after exercise and a similar reduction (P < 0.05) in the accumulation of inosine 5'-monophosphate and ammonia. During recovery, muscle inosine 5'-monophosphate (P < 0.05) and inosine (P < 0.01) content were reduced after training, as was the accumulation of inosine (P < 0.05). Plasma ammonia was higher (P < 0.05) after training early in recovery; in contrast, plasma hypoxanthine concentrations were reduced (P < 0.05) during the latter stages of recovery. The attenuated resting ATP and total adenine nucleotide contents after training probably result from the acute effects of prior training sessions. The reduction in the magnitude of ATP depletion during a 30-s sprint bout after training must reflect an improved balance between ATP hydrolysis and resynthesis. It is unclear which mechanism(s) is responsible for the reduction in the magnitude of ATP degradation after training.

Muscle adenine nucleotide metabolism during and in recovery from maximal exercise in humans.

The relationship between changes in the muscle total adenine nucleotide pool (TAN = ATP + ADP + AMP) and IMP during and after 30 s of sprint cycling was examined. Skeletal muscle samples were obtained from the vastus lateralis muscle of seven untrained men (23. 9 +/- 2.3 yr, 74.4 +/- 3.6 kg, and 55.0 +/- 2.9 ml. kg(-1). min(-1) peak oxygen consumption) before and immediately after exercise and after 5 and 10 min of passive recovery. The exercise-induced increase in muscle IMP was linearly related to the decrease in muscle TAN (r = -0.97, P < 0.01), and the slope of this relationship (-0.83) was not different from 1.0 (P > 0.05), indicating a 1:1 stoichiometric relationship. This interpretation must be treated cautiously, because all subjects displayed a greater decrease in TAN compared with the increase in IMP content, and the TAN + IMP + inosine + hypoxanthine content was lower (P < 0.05) immediately after exercise compared with during rest. During the first 5 min of recovery, the increase in TAN was not correlated with the decrease in IMP (r = -0.18, P > 0.05). In all subjects, the magnitude of TAN increase was higher than the magnitude of IMP decrease over this recovery period. In contrast, the increase in TAN was correlated with the decrease in IMP throughout the second 5 min of recovery (r = -0.80, P < 0.05), and it was a 1:1 stoichiometric relationship (slope = -1.12). These data indicate that a small proportion of the TAN pool was temporarily lost from the muscle purine stores during sprinting but was rapidly recovered after exercise.

Effect of carbohydrate ingestion on ammonia metabolism during exercise in humans.

The present study was undertaken to examine the effect of carbohydrate ingestion on plasma and muscle ammonia (NH(3) denotes ammonia and ammonium) accumulation during prolonged exercise. Eleven trained men exercised for 2 h at 65% peak pulmonary oxygen consumption while ingesting either 250 ml of an 8% carbohydrate-electrolyte solution every 15 min (CHO) or an equal volume of a sweet placebo. Blood glucose and plasma insulin levels during exercise were higher in CHO, but plasma hypoxanthine was lower after 120 min (1.7 +/- 0.3 vs. 2.6 +/- 0.1 micromol/l; P < 0. 05). Plasma NH(3) levels were similar at rest and after 30 min of exercise in both trials but were lower after 60, 90, and 120 min of exercise in CHO (62 +/- 9 vs. 76 +/- 9 micromol/l; P < 0.05). Muscle NH(3) levels were similar at rest and after 30 min of exercise but were lower after 120 min of exercise in CHO (1.51 +/- 0.21 vs. 2.07 +/- 0.23 mmol/kg dry muscle; P < 0.05; n = 5). These data are best explained by carbohydrate ingestion reducing muscle NH(3) production from amino acid degradation, although a small reduction in net AMP catabolism within the contracting muscle may also make a minor contribution to the lower tissue NH(3) levels.

Effect of heat stress on muscle energy metabolism during exercise.

To examine the effect of heat stress on muscle energy metabolism during submaximal exercise, 12 endurance-trained men cycled on two occasions for approximately 40 min at 70% maximal O2 uptake in an environmental chamber at either 20 degrees C and 20% relative humidity (T20) or 40 degrees C and 20% relative humidity (T40). Trials were conducted > or = 1 wk apart in random order. No difference in mean O2 uptake was observed when exercise in T40 was compared with that in T20. In contrast, exercise in T40 resulted in a higher mean heart rate (P < 0.01) and respiratory exchange ratio (P < 0.05) compared with that in T20. Postexercise rectal and muscle temperatures were also higher (P < 0.01) in T40 than in T20. Lower (P < 0.01) postexercise creatine phosphate and higher creatine (P < 0.01) and ammonia (P < 0.05) were observed in muscle after exercise in T40 compared with T20. In addition, an increased (P < 0.01) muscle glycogenolysis and higher (P < 0.01) postexercise muscle lactate accumulation were observed during exercise in T40 compared with T20. In contrast, no differences were observed in postexercise concentrations of total adenine nucleotide pool (ATP+ADP+AMP), ATP/ADP ratio, or inosine 5'-monophosphate (IMP) when T40 was compared with T20. These results indicate that the rate of ATP utilization may be increased during exercise in the heat but that this increased energy demand is predominantly met by an increase in anaerobic glycolysis and creatine phosphate hydrolysis, preventing a reduction in total adenine nucleotide pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of creatine supplementation on sprint exercise performance and muscle metabolism.

The aim of the present study was to examine the effect of creatine supplementation (CrS) on sprint exercise performance and skeletal muscle anaerobic metabolism during and after sprint exercise. Eight active, untrained men performed a 20-s maximal sprint on an air-braked cycle ergometer after 5 days of CrS [30 g creatine (Cr) + 30 g dextrose per day] or placebo (30 g dextrose per day). The trials were separated by 4 wk, and a double-blind crossover design was used. Muscle and blood samples were obtained at rest, immediately after exercise, and after 2 min of passive recovery. CrS increased the muscle total Cr content (9.5 +/- 2.0%, P < 0.05, mean +/- SE); however, 20-s sprint performance was not improved by CrS. Similarly, the magnitude of the degradation or accumulation of muscle (e.g., adenine nucleotides, phosphocreatine, inosine 5'-monophosphate, lactate, and glycogen) and plasma metabolites (e.g. , lactate, hypoxanthine, and ammonia/ammonium) were also unaffected by CrS during exercise or recovery. These data demonstrated that CrS increased muscle total Cr content, but the increase did not induce an improved sprint exercise performance or alterations in anaerobic muscle metabolism.

Muscle metabolites and performance during high-intensity, intermittent exercise.

Six men were studied during four 30-s "all-out" exercise bouts on an air-braked cycle ergometer. The first three exercise bouts were separated by 4 min of passive recovery; after the third bout, subjects rested for 4 min, exercised for 30 min at 30-35% peak O2 consumption, and rested for a further 60 min before completing the fourth exercise bout. Peak power and total work were reduced (P < 0. 05) during bout 3 [765 +/- 60 (SE) W; 15.8 +/- 1.0 kJ] compared with bout 1 (1,168 +/- 55 W, 23.8 +/- 1.2 kJ), but no difference in exercise performance was observed between bouts 1 and 4 (1,094 +/- 64 W, 23.2 +/- 1.4 kJ). Before bout 3, muscle ATP, creatine phosphate (CP), glycogen, pH, and sarcoplasmic reticulum (SR) Ca2+ uptake were reduced, while muscle lactate and inosine 5'-monophosphate were increased. Muscle ATP and glycogen before bout 4 remained lower than values before bout 1 (P < 0.05), but there were no differences in muscle inosine 5'-monophosphate, lactate, pH, and SR Ca2+ uptake. Muscle CP levels before bout 4 had increased above resting levels. Consistent with the decline in muscle ATP were increases in hypoxanthine and inosine before bouts 3 and 4. The decline in exercise performance does not appear to be related to a reduction in muscle glycogen. Instead, it may be caused by reduced CP availability, increased H+ concentration, impairment in SR function, or some other fatigue-inducing agent.